Genetically hypertensive rats have been widely described as the animal model most closely resembling human essential hypertension; however, assessment of this statement can not be made until mechanisms underlying the cause of development and maintenance of hypertension in these animals have been fully defined. During pregnancy and pseudopregancy blood pressure of New Zealand genetically hypertensive (NZGH) rats is transiently reduced to normotensive levels; we will investigate the mechanism responsible for this normalization of blood pressure in relation to the maintenance of hypertension in the NZGH rats. Possible involvement of the renin-angiotensin system, prostaglindins, and sex hormones will be assessed. Renal denervation of young NZGH rats delays the development of hypertension. We will determine whether renal denervation alters blood pressure development also in normotensive rats, determine the effect of renal denervation on the renal arterial pressure-urinary sodium excretion relation, and utilize renal denervated rats to establish whether the hyperresponsiveness to vasopressor stimuli, exhibited by NZGH rats, is an inherent characteristic or one dependent on differences in blood pressure. Renal vascular resistance is elevated in NZGH rats; we will quantitate the contribution of renal nerve activity, renal responsiveness to nerve stimulation, intrarenal prostaglandins, and renal vascular structure to the renal resistance elevation. Activity of renal 15-hydroxyprostaglandin dehydrogenase (PGDH) is much lower in kidneys of female rats than in those of males; the effect of this difference on renal vascular responsiveness to exogenous prostaglandins will be determined. Addition of homogenates of female rat kidneys to homogenates of male rat kidneys suppresses the activity of PGDH in the latter; we will determine if this is the result of an endogenous inhibitor substance and, if so, isolate and characterize the inhibitor. In the dog, the relationship between renal arterial pressure, renal vascular resistance, and intrarenal prostaglandins will be determined. In the rat, the contribution of renal prostaglandins to determination of renal resistance during hemorrhage will be evaluated.